title: Sporadic obstructive hydrocephalus in Aqp4 null mice.
abstract: Aquaporin-4 (Aqp4) is a water transport protein expressed in glia and ependymocytes in brain. We report here the unexpected occurrence of severe obstructive hydrocephalus in a random subset of Aqp4 knockout mice. Of 612 Aqp4 knockout mice produced by heterozygote-heterozygote or knockout-knockout breedings, 9.6% of offspring manifested progressive encephalomegaly. Encephalomegaly was never seen in wild-type or Aqp4 heterozygous mice. Examination of the subset encephalomegalic mice revealed marked triventricular hydrocephalus (lateral ventricle size approximately 500 mm(3)), elevated intracranial pressure (19 +/- 3 vs. 6.1 +/- 0.6 mm Hg), and death by age 6 weeks, with a median survival of 28 days. Intraventricular dye injection studies revealed total obstruction of the cerebral aqueduct. Evans blue extravasation studies indicated an intact blood-brain barrier in the hydrocephalic mice. Brain histology revealed reduced ventricular size and ependymocyte disorganization in some nonhydrocephalic Aqp4 null mice. Our studies establish Aqp4 deletion as a predisposing factor for the development of congenital obstructive hydrocephalus in mice. We suggest that AQP4 polymorphisms might also contribute to the development of aqueduct stenosis in humans.
authors.affiliation: Membrane Channel Research Laboratory and Key Laboratory for Applied Statistics of MOE, Northeast Normal University, Changchun, P.R. China.
authors.forename: Xuechao
authors.initials: X
authors.lastname: Feng
authors.forename: Marios C
authors.initials: MC
authors.lastname: Papadopoulos
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Lihua
authors.initials: L
authors.lastname: Li
authors.forename: Di
authors.initials: D
authors.lastname: Zhang
authors.forename: Hongguo
authors.initials: H
authors.lastname: Zhang
authors.forename: A S
authors.initials: AS
authors.lastname: Verkman
authors.forename: Tonghui
authors.initials: T
authors.lastname: Ma
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics*; D001812:Blood-Brain Barrier / Q000473:pathology; D002535:Cerebral Aqueduct / Q000473:pathology; D002552:Cerebral Ventricles / Q000473:pathology*; D003251:Constriction, Pathologic; D004805:Ependyma / Q000473:pathology; D005070:Evans Blue; D005119:Extravasation of Diagnostic and Therapeutic Materials; D020022:Genetic Predisposition to Disease; D006849:Hydrocephalus / Q000235:genetics* / Q000401:mortality; D007276:Injections, Intraventricular; D007427:Intracranial Pressure / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout
chemical_list: C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D005070:Evans Blue